Aberrant FAM135B attenuates the efficacy of chemotherapy in colorectal cancer by modulating SRSF1-mediated alternative splicing.

Oxaliplatin is the frontline chemotherapy drug for the treatment of colorectal cancer (CRC) and its insensitivity is a major limitation on therapeutic efficacy. Genomic instability is the prominent feature of CRC and is considered to correlate with response to treatments. However, the underlying mechanism of insensitivity to oxaliplatin (L-OHP) remains largely unclear. Herein, sequence similarity 135 family member B (FAM135B) is identified as a frequently mutated gene in CRC and is critical for CRC proliferation and impaired response to L-OHP by controlling SRSF1-mediated alternative splicing. Specifically, FAM135B promotes the nuclear translocation of SRSF1 by synergistically binding with SRPK1 and regulates SRSF1-mediated splicing of DNA repair genes. FAM135B-induced exon IV inclusion of FAAP20 mediates its binding with FACNA and enhances the functional integrity of the FA core complex, thereby activating the FA pathway and resulting in inter-strand crosslink (ICL) lesion repair and L-OHP insensitivity. These findings reveal that the FAM135B-SRSF1 axis-mediated splicing contributes to DNA repair and chemotherapeutic insensitivity in CRC. Targeting FAM135B represents a potential strategy for CRC treatment.

Heterozygous de novo dominant negative mutation of REXO2 results in interferonopathy.

Mitochondrial RNA (mtRNA) in the cytosol can trigger the innate immune sensor MDA5, and autoinflammatory disease due to type I IFN. Here, we show that a dominant negative mutation in the gene encoding the mitochondrial exonuclease REXO2 may cause interferonopathy by triggering the MDA5 pathway. A patient characterized by this heterozygous de novo mutation (p.T132A) presented with persistent skin rash featuring hyperkeratosis, parakeratosis and acanthosis, with infiltration of lymphocytes and eosinophils around small blood vessels. In addition, circulating IgE levels and inflammatory cytokines, including IFNα, are found consistently elevated. Transcriptional analysis highlights a type I IFN gene signature in PBMC. Mechanistically, REXO2 (T132A) lacks the ability to cleave RNA and inhibits the activity of wild-type REXO2. This leads to an accumulation of mitochondrial dsRNA in the cytosol, which is recognized by MDA5, leading to the associated type I IFN gene signature. These results demonstrate that in the absence of appropriate regulation by REXO2, aberrant cellular nucleic acids may accumulate and continuously trigger innate sensors, resulting in an inborn error of immunity.

Potassium Ion-Assisted Self-Assembled MXene-K-CNT Composite as High-Quality Sulfur-Loaded Hosts for Lithium-Sulfur Batteries.

We successfully synthesized hybrid MXene-K-CNT composites composed of alkalized two-dimensional (2D) metal carbide and carbon nanotubes (CNTs), which were employed as host materials for lithium-sulfur (Li-S) battery cathodes. The unique three-dimensional (3D) intercalated structure through electrostatic interactions by K+ ions in conjunction with the scaffolding effect provided by CNTs effectively inhibited the self-stacking of MXene nanosheets, resulting in an enhanced specific surface area (SSA) and ion transport capability. Moreover, the addition of CNTs and in situ-grown TiO2 considerably improved the conductivity of the cathode material. K+ ion etching created a more hierarchical porous structure in MXene, which further enhanced the SSA. The 3D framework effectively confined S embedded between nanosheet layers and suppressed volume changes of the cathode composite during charging/discharging processes. This combination of CNTs and alkalized nanosheets functioned as a physical and chemical dual adsorption system for lithium polysulfides (LiPSs). When subjected to a high current at 1.0C, S@MXene-K-0.5CNT with S-loaded of 1.2 mg cm-2 had an initial capacity of 919.6 mAh g-1 and capacity decay rate of merely 0.052% per cycle after 1000 cycles. Moreover, S@MXene-K-0.5CNT maintained good cycling stability even at a high current of up to 5.0C. These impressive results highlight the potential of alkalized 2D MXene nanosheets intercalated with CNTs as highly promising cathode materials for Li-S batteries. The study findings also have prospects for the development of next-generation Li-S batteries with high energy density and prolonged lifespans.

Knowledge, attitude, and practice toward photoaging in the Chinese population: a cross-sectional study.

To investigate the knowledge, attitude, and practice (KAP) of photoaging in the Chinese population. This web-based cross-sectional study was conducted between January 2023 and March 2023 among the Chinese population aged 18-80 years old. Participants' knowledge, attitude, and practice toward photoaging were collected through a self-administered questionnaire. A total of 830 questionnaires were collected, with 826 valid questionnaires and an efficiency rate of 99.52%. There were 274 (33.17%) males and 532 (64.41%) aged 31-51 years old. The average knowledge, attitude, and practice scores were 7 (4, 9) (possible range 0-12), 31.5 (28, 34) (possible range 8-40), and 33 (24, 42) (possible range 11-55), respectively, indicating poor knowledge, good attitude, and moderate practice. Spearman correlation analysis showed that knowledge was negatively correlated with attitude (r = - 0.111, P < 0.05) and practice (r = - 0.113, P < 0.05), and attitude was positively correlated with practice (r = 0.992, P < 0.05). The multivariable linear regression model showed that for each point increase in attitude score, the practice score increased by 2.96 points (ß = 2.96, 95% CI 2.91-3.01, P < 0.001). The Chinese population has poor knowledge, good attitude, and moderate practice toward photoaging. A good attitude toward photoaging would lead to good practice, and more outreach and education for the Chinese population might be needed.

G3BP1 and SLU7 Jointly Promote Immune Evasion by Downregulating MHC-I via PI3K/Akt Activation in Bladder Cancer.

Immune checkpoint inhibitors (ICIs) show promise as second-line treatment for advanced bladder cancer (BLCA); however, their responsiveness is limited by the immune evasion mechanisms in tumor cells. This study conduct a Cox regression analysis to screen mRNA-binding proteins and reveals an association between Ras GTPase-activating protein-binding protein 1 (G3BP1) and diminished effectiveness of ICI therapy in patients with advanced BLCA. Subsequent investigation demonstrates that G3BP1 enhances immune evasion in BLCA cells by downregulating major histocompatibility complex class I (MHC-I) through phosphoinositide 3-kinase (PI3K)/Akt signaling activation. Mechanistically, G3BP1 interacts with splicing factor synergistic lethal with U5 snRNA 7 (SLU7) to form a complex with poly(A)-binding protein cytoplasmic 1 and eukaryotic translation initiation factor 4 gamma 1. This complex stabilizes the closed-loop structure of the mRNAs of class IA PI3Ks and consequently facilitates their translation and stabilization, thereby activating PI3K/Akt signaling to downregulate MHC-I. Consistently, targeting G3BP1 with epigallocatechin gallate (EGCG) impedes immune evasion and sensitizes BLCA cells to anti-programmed cell death (PD)-1 antibodies in mice. Thus, G3BP1 and SLU7 collaboratively contribute to immune evasion in BLCA, indicating that EGCG is a precision therapeutic agent to enhance the effectiveness of anti-PD-1 therapy.

Does microneedle fractional radiofrequency system inactivate botulinum toxin type A?

BACKGROUND: The combination of botulinum toxin type A (BoNT/A) and energy equipment have been widely used in the clinic. AIMS: To determine whether the energy of microneedle fractional radiofrequency (MFR) affects the efficacy of BoNT/A and to provide an optimal strategy for the energy device in combination with BoNT/A in the clinic. METHODS: First, a total of 45 females with moderate-to-severe periorbital crow's feet wrinkles were enrolled and divided into three groups according to different treatment methods and intervals, including BoNT/A injection alone, BoNT/A injected immediately after MFR treatment and BoNT/A injected 7 days after MFR treatment. The photographs were compared before treatment and 4 weeks after treatment. Then, the mouse models were established by combining MFR with BoNT/A at different intervals, to evaluate muscle strength, muscle mass, muscle nutritional markers, and important cytokines levels. RESULTS: All patients in each group had high satisfaction. The MFR + BoNT/A (immediately) group could improve dynamic wrinkles, but the others had more significant efficacy (p < 0.05). The results of mouse models showed that all BoNT/A groups induced different degrees of muscle paralysis in vivo, but the paralytic effect induced by the BoNT/A group, MFR + BoNT/A (interval of 3-day) group, and MFR + BoNT/A (interval of 7-day) group were higher than others and the expression levels of muscle nutritional markers in NMJ tissues were significantly upregulated. CONCLUSION: MFR has a certain reduction effect on the activity of BoNT/A, and this reduction effect would last for 3 days after MFR treatment.

Differential Diagnosis of Rosacea Using Machine Learning and Dermoscopy.

Introduction: Rosacea is a common chronic inflammatory disease occurring on the face, whose diagnosis is mainly based on symptoms and physical signs. Due to some overlap in symptoms and signs with other inflammatory skin diseases, young and inexperienced doctors often make misdiagnoses and missed diagnoses in clinical practices. We analyze the results of skin physiology and dermatoscopy using machine learning method and identify the characteristics of acne rosacea, which differentiate it from other common facial inflammatory skin diseases so as to improve the accuracy of clinical and differential diagnosis of rosacea. Methods: A total of 495 patients who were jointly diagnosed by two experienced doctors were included. Basic data, clinical symptoms, physiological skin detection, and dermatoscopy results were collected, and the clinical characteristics of rosacea and other common facial inflammatory diseases were summarized according to the descriptive analysis results. The model was established using a machine learning method and compared with the judgment results of young and inexperienced doctors to verify whether the model can improve the accuracy of clinical diagnosis and differential diagnosis of rosacea. Results: The proportion of yellow and red halos, vascular polygons, as well as follicular pustules, showed by dermatoscopy, and the melanin index in physiological skin detection revealed statistical significance in differentiating rosacea and other common facial inflammatory diseases (all P < 0.01). After adopting the machine learning, we found that GBM (Gradient Boosting Machine) algorithm was the best, and the error rate of this model in the validation set was 5.48%. In the final man-machine comparison, the accuracy of the GBM algorithm model for the classification of skin disease was significantly higher than that of young and inexperienced doctors. Conclusion: Dermatoscopy combined with machine learning can effectively improve the diagnosis and differential diagnosis accuracy of rosacea and other facial inflammatory skin diseases.

Multi-Role Surface Modification of Single-Crystalline Nickel-Rich Lithium Nickel Cobalt Manganese Oxides Cathodes with WO3 to Improve Performance for Lithium-Ion Batteries.

Compared with the polycrystalline system, the single-crystalline ternary cathode material has better cycle stability because the only primary particles without grain boundaries effectively alleviate the formation of micro/nanocracks and retain better structural integrity. Therefore, it has received extensive research attention. There is no consistent result whether tungsten oxide acts as doping and/or coating from the surface modification of the polycrystalline system. Meanwhile, there is no report on the surface modification of the single-crystalline system by tungsten oxide. In this paper, multirole surface modification of single-crystalline nickel-rich ternary cathode material LiNi0.6Co0.2Mn0.2O2 by WO3 is studied by a simple method of adding WO3 followed by calcination. The results show that with the change in the amount of WO3 added, single-crystalline nickel-rich ternary cathode material can be separately doped, separately coated, and both doped and coated. Either doping or coating effectively enhances the structural stability, reduces the polarization of the material, and improves the lithium-ion diffusion kinetics, thus improving the cycle stability and rate performance of the battery. Interestingly, both doping and coating (for SC-NCM622-0.5%WO3) do not show a more excellent synergistic effect, while the single coating (for SC-NCM622-1.0%WO3) after eliminating the rock-salt phase layer performs the most excellent modification effect.